Trial reportThe Journal of biological chemistry2014
Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-β (TGF-β) signaling promoting SMAD3 activation and fibrosis via Gremlin protein.
Trial report in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
147 citing papers in PubMed, 239 citations in OpenAlex.
- Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis.Annals of the rheumatic diseases · 2018Trial
- Trial
- Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.Ageing research reviews · 2026Review
- Sciatic denervation differentially remodels skeletal muscle and deep fascia in the lower limb of male mice.Physiological reports · 2026Article
- TNFα drives disease-specific chemokine networks and orbital tissue remodeling in a preclinical model of thyroid eye disease.European thyroid journal · 2026Article
- Inflammatory and hormonal crosstalk linking rheumatic fever to chronic valvular heart disease.Molecular biology reports · 2026Review
- Longitudinal clinical response to Janus kinase inhibitors in systemic sclerosis: a real-life multicentric study across multiple clinical domains.Clinical rheumatology · 2026Article
- Senescence intensifies bleomycin-induced injury in idiopathic pulmonary fibrosis lung epithelial cells.ERJ open research · 2026Article
- Article
- Review
- Characterization of KLK5-high epithelial cells and their interactions with the tumor microenvironment in high-grade serous ovarian cancer.Cancer cell international · 2026Article
- Cadherin-11 integrates Piezo1 and interleukin-6 signaling to promote fibroblast activation.Biomaterials science · 2026Article
- Validation of Indocyanine Green-Methylene Blue Dye in the Lymphedema Rat Tail Model.Biomedicines · 2026Article
- Dysregulation of MMP-2 and MMP-9 in Post-COVID-19 and IPF: Correlations with Systemic Inflammation and Endothelial Dysfunction.Journal of clinical medicine · 2026Article
- Pyruvate kinase M2 is elevated in systemic sclerosis and plays a role in its pathogenesis.Frontiers in immunology · 2026Article
- Long-term cytokine exposure remodels the methylome and transcriptome of recessive dystrophic epidermolysis bullosa keratinocytes - a bioinformatic analysis.Frontiers in cell and developmental biology · 2026Article
- Divergent immune and extracellular matrix transcriptional programs underlie poor prognosis in early-stage lung adenocarcinoma.Frontiers in immunology · 2026Article
- Characterization of cancer-associated fibroblast populations that promote tertiary lymphoid structure formation in murine melanoma tumors.Frontiers in immunology · 2026Article
- The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair.Biomedicines · 2025Review
- Advances in the Molecular Mechanisms of Pulmonary Fibrosis in Systemic Sclerosis: A Comprehensive Review.International journal of molecular sciences · 2025Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis is a common and intractable condition associated with various pathologies. It is characterized by accumulation of an excessive amount of extracellular matrix molecules that primarily include collagen type I. IL-6 is a profibrotic cytokine that is elevated in the prototypic fibrotic autoimmune condition systemic sclerosis and is known to induce collagen I expression, but the mechanism(s) behind this induction are currently unknown. Using healthy dermal fibroblasts in vitro, we analyzed the signaling pathways that underscore the IL-6-mediated induction of collagen. We show that IL-6 trans signaling is important and that the effect is dependent on STAT3; however, the effect is indirect and mediated through enhanced TGF-β signaling and the classic downstream cellular mediator Smad3. This is due to induction of the bone morphogenetic protein (BMP) antagonist Gremlin-1, and we show that Gremlin-1 is profibrotic and is mediated through canonical TGF-β signaling.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.